المؤلفون: Vogelezang, S., Bradfield, J.P., Ahluwalia, T.S., Curtin, J.A., Lakka, T.A., Grarup, N., Scholz, M., van der Most, P.J., Monnereau, C., Stergiakouli, E., Heiskala, A., Horikoshi, M., Fedko, I.O., Vilor-Tejedor, N., Cousminer, D.L., Standl, M., Wang, C.A., Viikari, J., Geller, F., Íñiguez, C., Pitkänen, N., Chesi, A., Bacelis, J., Yengo, L., Torrent, M., Ntalla, I., Helgeland, Ø., Selzam, S., Vonk, J.M., Zafarmand, M.H., Heude, B., Farooqi, I.S., Alyass, A., Beaumont, R.N., Have, C.T., Rzehak, P., Bilbao, J.R., Schnurr, T.M., Barroso, I., Bønnelykke, K., Beilin, L.J., Carstensen, L., Charles, M.A., Chawes, B., Clément, K., Closa-Monasterolo, R., Custovic, A., Eriksson, J.G., Escribano, J., Groen-Blokhuis, M., Grote, V., Gruszfeld, D., Hakonarson, H., Hansen, T., Hattersley, A.T., Hollensted, M., Hottenga, J.J., Hyppönen, E., Johansson, S., Joro, R., Kähönen, M., Karhunen, V., Kiess, W., Knight, B.A., Koletzko, B., Kühnapfel, A., Landgraf, K., Langhendries, J.P., Lehtimäki, T., Leinonen, J.T., Li, A., Lindi, V., Lowry, E., Bustamante, M., Medina-Gomez, C., Melbye, M., Michaelsen, K.F., Morgen, C.S., Mori, T.A., Nielsen, T.R.H., Niinikoski, H., Oldehinkel, A.J., Pahkala, K., Panoutsopoulou, K., Pedersen, O., Pennell, C.E., Power, C., Reijneveld, S.A., Rivadeneira, F., Simpson, A., Sly, P.D., Stokholm, J., Teo, K.K., Thiering, E., Timpson, N.J., Uitterlinden, A.G., Zeggini, E., van Beijsterveldt, C.E.M., van Schaik, B.D.C., Vaudel, M., Verduci, E.

المصدر: PLoS Genet. 16:e1008718 (2020)

الوصف: The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological ...

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33045005; info:eu-repo/semantics/altIdentifier/wos/WOS:000582197600001; info:eu-repo/semantics/altIdentifier/isbn/1553-7390; info:eu-repo/semanti; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60367Test; urn:isbn:1553-7390; urn:issn:1553-7390; urn:issn:1553-7404

الإتاحة: https://doi.org/10.1371/journal.pgen.1008718Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60367Test

المؤلفون: Bradfield, J.P., Vogelezang, S., Felix, J.F., Chesi, A., Helgeland, Ø., Horikoshi, M., Karhunen, V., Lowry, E., Cousminer, D.L., Ahluwalia, T.S., Thiering, E., Boh, E.T., Zafarmand, M.H., Wang, C.A., Joro, R., Chen, Z., Gauderman, W.J., Pitkänen, N., Parra, E.J., Fernández-Rhodes, L., Alyass, A., Monnereau, C., Curtin, J.A., Have, C.T., McCormack, S.E., Hollensted, M., Frithioff-Bøjsøe, C., Valladares-Salgado, A., Peralta-Romero, J., Standl, M., Leinonen, J.T., Holm, J.C., Peters, T., Vioque, J., Vrijheid, M., Simpson, A., Custovic, A., Vaudel, M., Canouil, M., Lindi, V., Atalay, M., Kähönen, M., Raitakari, O.T., van Schaik, B.D.C., Berkowitz, R.I., Cole, S.A., Voruganti, V.S., Wang, Y., Highland, H.M., Comuzzie, A.G., Butte, N.F., Justice, A.E., Gahagan, S., Blanco, E., Lehtimäki, T., Lakka, T.A., Hebebrand, J., Bonnefond, A., Grarup, N., Froguel, P., Lyytikäinen, L.P., Cruz, M., Kobes, S., Hanson, R.L., Zemel, B.S., Hinney, A., Teo, K.K., Meyre, D., North, K.E., Gilliland, F.D., Bisgaard, H., Bustamante, M., Bonnelykke, K., Pennell, C.E., Rivadeneira, F., Uitterlinden, A.G., Baier, L.J., Vrijkotte, T.G.M., Heinrich, J., Sørensen, T.I.A., Saw, S.M., Pedersen, O., Hansen, T., Eriksson, J., Widén, E., McCarthy, M.I., Njølstad, P.R., Power, C., Hyppönen, E., Sebert, S., Brown, C.D., Timpson, N.J., Johansson, S., Hakonarson, H., Jaddoe, V.W.V.

المصدر: Hum. Mol. Genet. 28, 3327-3338 (2019)

الوصف: Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13005 cases (>= 95th percentile of body mass index (BMI) achieved 2-18 years old) and 15599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31504550; info:eu-repo/semantics/altIdentifier/wos/WOS:000501731100016; info:eu-repo/semantics/altIdentifier/isbn/0964-6906; info:eu-repo/semantics/altIden; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=56859Test; urn:isbn:0964-6906; urn:issn:0964-6906; urn:issn:1460-2083

الإتاحة: https://doi.org/10.1093/hmg/ddz161Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=56859Test

المؤلفون: Warrington, N.M., Beaumont, R.N., Horikoshi, M., Day, F.R., Helgeland, Ø., Laurin, C., Bacelis, J., Peng, S., Hao, K., Feenstra, B., Wood, A.R., Mahajan, A., Tyrrell, J., Robertson, N.R., Rayner, N.W., Qiao, Z., Moen, G.H., Vaudel, M., Marsit, C.J., Chen, J., Nodzenski, M., Schnurr, T.M., Zafarmand, M.H., Bradfield, J.P., Grarup, N., Kooijman, M.N., Li-Gao, R., Geller, F., Ahluwalia, T.S., Paternoster, L., Rueedi, R., Huikari, V., Hottenga, J.J., Lyytikäinen, L.P., Cavadino, A., Metrustry, S., Cousminer, D.L., Wu, Y., Thiering, E., Wang, C.A., Have, C.T., Vilor-Tejedor, N., Joshi, P.K., Painter, J.N., Ntalla, I., Myhre, R., Pitkänen, N., van Leeuwen, E.M., Joro, R., Lagou, V., Richmond, R.C., Espinosa, A., Barton, S.J., Inskip, H.M., Holloway, J.W., Santa-Marina, L., Estivill, X., Ang, W., Marsh, J.A., Reichetzeder, C., Marullo, L., Hocher, B., Lunetta, K.L., Murabito, J.M., Relton, C.L., Kogevinas, M., Chatzi, L., Allard, C., Bouchard, L., Hivert, M.F., Zhang, G., Muglia, L.J., Heikkinen, J., Morgen, C.S., van Kampen, A.H.C., van Schaik, B.D.C., Mentch, F.D., Langenberg, C., Luan, J., Scott, R.A., Zhao, J.H., Hemani, G., Ring, S.M., Bennett, A.J., Gaulton, K.J., Fernandez-Tajes, J., van Zuydam, N.R., Medina-Gomez, C., de Haan, H.G., Rosendaal, F.R., Kutalik, Z., Marques-Vidal, P., Das, S., Willemsen, G., Mbarek, H., Müller-Nurasyid, M., Standl, M., Appel, E.V.R., Fonvig, C.E., Trier, C., van Beijsterveldt, C.E.M., Murcia, M., Bustamante, M., Bonàs-Guarch, S., Hougaard, D.M., Mercader, J.M., Linneberg, A., Schraut, K.E., Lind, P.A., Medland, S.E., Shields, B.M., Knight, B.A., Chai, J.F., Panoutsopoulou, K., Bartels, M., Sánchez, F., Stokholm, J., Torrents, D., Vinding, R.K., Willems, S.M., Atalay, M., Chawes, B.L., Kovacs, P., Prokopenko, I., Tuke, M.A., Yaghootkar, H., Ruth, K.S., Jones, S.E., Loh, P.R., Murray, A., Weedon, M.N., Tönjes, A., Stumvoll, M., Michaelsen, K.F., Eloranta, A.M., Lakka, T.A., van Duijn, C.M., Kiess, W., Körner, A., Niinikoski, H., Pahkala, K., Raitakari, O.T., Jacobsson, B., Zeggini, E., Dedoussis, G.V., Teo, Y.Y., Saw, S.M., Montgomery, G.W., Campbell, H., Wilson, J.F., Vrijkotte, T.G.M., Vrijheid, M., de Geus, E.J.C.N., Hayes, M.G., Kadarmideen, H.N., Holm, J.C., Beilin, L.J., Pennell, C.E., Heinrich, J., Adair, L.S., Borja, J.B., Mohlke, K.L., Eriksson, J.G., Widén, E.E., Hattersley, A.T., Spector, T.D., Kähönen, M., Viikari, J.S., Lehtimäki, T., Boomsma, D.I., Sebert, S., Vollenweider, P., Sørensen, T.I.A., Bisgaard, H., Bønnelykke, K., Murray, J.C., Melbye, M., Nohr, E.A., Mook-Kanamori, D.O., Rivadeneira, F., Hofman, A., Felix, J.F., Jaddoe, V.W.V., Hansen, T., Pisinger, C., Vaag, A.A., Pedersen, O., Uitterlinden, A.G., Järvelin, M.R., Power, C., Hyppönen, E., Scholtens, D.M., Lowe, W.L., Davey Smith, G., Timpson, N.J., Morris, A.P., Wareham, N.J., Hakonarson, H., Grant, S.F.A., Frayling, T.M., Lawlor, D.A., Njølstad, P.R., Johansson, S., Ong, K.K., McCarthy, M.I., Perry, J.R.B., Evans, D.M., Freathy, R.M.

المصدر: Nat. Genet. 51, 804-814 (2019)

الوصف: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31043758; info:eu-repo/semantics/altIdentifier/wos/WOS:000466842000008; info:eu-repo/semantics/altIdentifier/isbn/1061-4036; info:eu-repo/semantics/; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=55978Test; urn:isbn:1061-4036; urn:issn:1061-4036; urn:issn:1546-1718

الإتاحة: https://doi.org/10.1038/s41588-019-0403-1Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=55978Test

المؤلفون: Francioli, L.C., Polak, P.P., Koren, A., Menelaou, A., Chun, S., Renkens, I., van Duijn, C.M., Swertz, M.A., Wijmenga, C., van Ommen, G.J., Slagboom, P.E., Boomsma, D.I., Ye, K., Guryev, V., Arndt, P.F., Kloosterman, W.P., Bakker, P.I.W., Sunyaev, S.R., Dijk, F., Neerincx, P.B.T., Pulit, S.L., Deelen, P., Elbers, C.C., Palamara, P.F., Pe'er, I., Abdellaoui, A., van Oven, M., Vermaat, M., Li, M., Laros, J.F.J., Stoneking, M., de Knijff, P., Kayser, M., Veldink, J.H., Van den Berg, L.H., Byelas, H., den Dunnen, J.T., Dijkstra, M., Amin, N., van der Velde, K.J., Hottenga, J.J., van Setten, J., van Leeuwen, E.M., Kanterakis, A., Kattenberg, V.M., Karssen, L.C., van Schaik, B.D.C., Bot, J., Nijman, I.J., van Enckevort, D., Mei, H., Koval, V., Estrada, K., Medina-Gomez, C., Lameijer, E.W., Moed, M.H., Hehir-Kwa, J.Y., Handsaker, R.E., McCarroll, S.A., Vuzman, D., Sohail, M., Hormozdiari, F., Marschall, T., Schönhuth, A., Beekman, M., de Craen, A.J., Suchiman, H.E.D., Hofman, A., Oostra, B., Isaacs, A., Rivadeneira, F., Uitterlinden, A.G., Willemsen, G., Platteel, M., Pitts, S.J., Potluri, S., Sundar, P., Cox, D.R., Li, Q., Li, Y., Du, Y., Chen, R., Cao, H., Li, N., Cao, S., Wang, J., Bovenberg, J.A., Brandsma, M.

المصدر: Francioli , L C , Polak , P P , Koren , A , Menelaou , A , Chun , S , Renkens , I , van Duijn , C M , Swertz , M A , Wijmenga , C , van Ommen , G J , Slagboom , P E , Boomsma , D I , Ye , K , Guryev , V , Arndt , P F , Kloosterman , W P , Bakker , P I W , Sunyaev , S R , Dijk , F , Neerincx , P B T , Pulit , S ....

مصطلحات موضوعية: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_, name=Netherlands Twin Register (NTR)

الوصف: Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of older fathers are not only more numerous but also occur more frequently in early-replicating, genic regions. Functional regions exhibit higher mutation rates due to CpG dinucleotides and show signatures of transcription-coupled repair, whereas mutation clusters with a unique signature point to a new mutational mechanism. Mutation and recombination rates independently associate with nucleotide diversity, and regional variation in human-chimpanzee divergence is only partly explained by heterogeneity in mutation rate. Finally, we provide a genome-wide mutation rate map for medical and population genetics applications. Our results provide new insights and refine long-standing hypotheses about human mutagenesis.

العلاقة: https://research.vu.nl/en/publications/66af59bc-601b-41a7-be58-fe092af15064Test

الإتاحة: https://doi.org/10.1038/ng.3292Test
https://research.vu.nl/en/publications/66af59bc-601b-41a7-be58-fe092af15064Test
https://hdl.handle.net/1871.1/66af59bc-601b-41a7-be58-fe092af15064Test

المؤلفون: Francioli, L.C., Menelaou, A., Pulit, S.L., Dijk, F., Palamara, P.F., Elbers, C.C., Neerincx, P.B.T., Ye, K., Guryev, V., Kloosterman, W.P., Deelen, P., Abdellaoui, A., van Leeuwen, E., van Oven, M., Vermaat, M., Li, M., Laros, J.F.J., Karssen, L.C., Kanterakis, A., Amin, N., Lameijer, E.W., Kattenberg, V.M., Dijkstra, M., Byelas, H., van Setten, J., van Schaik, B.D.C., Bot, J., Nijman, I.J., Renkens, I., Marschall, T., Schönhuth, A., Hehir-Kwa, J.Y., Handsaker, R.E., Polak, P., Sohail, M., Vuzman, D., Hormozdiari, F., van Enckevort, D., Mei, H., Koval, V., Moed, M.H., van der Velde, K.J., Rivadeneira, F., Estrada, K., Medina-Gomez, C., Isaacs, A., McCarroll, S.A., Beekman, M., de Craen, A.J., Suchiman, H.E.D., Hofman, A., Oostra, B.A., Uitterlinden, A.G., Willemsen, G., Platteel, M., Veldink, J.H., Van den Berg, L.H., Pitts, S.J., Potluri, S., Sundar, P., Cox, D.R., Sunyaev, S.R., den Dunnen, J.T., Stoneking, M., de Knijff, P., Kayser, M., Li, Q., Li, Y., Du, Y., Chen, R., Cao, H., Li, N., Cao, S., Wang, J., Bovenberg, J.A., Pe'er, I., Slagboom, P.E., van Duijn, C.M., Boomsma, D.I., van Ommen, G.J.B, Bakker, P.I.W., Swertz, M., Wijmenga, C.

المصدر: Francioli , L C , Menelaou , A , Pulit , S L , Dijk , F , Palamara , P F , Elbers , C C , Neerincx , P B T , Ye , K , Guryev , V , Kloosterman , W P , Deelen , P , Abdellaoui , A , van Leeuwen , E , van Oven , M , Vermaat , M , Li , M , Laros , J F J , Karssen , L C , Kanterakis , A , Amin , N , Lameijer , E W , Kattenberg , ....

مصطلحات موضوعية: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_, name=Netherlands Twin Register (NTR), /dk/atira/pure/sustainabledevelopmentgoals/life_below_water, name=SDG 14 - Life Below Water

الوصف: Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies. © 2014 Nature America, Inc.

العلاقة: https://research.vu.nl/en/publications/20ebcf66-2f57-433e-84da-f9b4bdad9754Test

الإتاحة: https://doi.org/10.1038/ng.3021Test
https://research.vu.nl/en/publications/20ebcf66-2f57-433e-84da-f9b4bdad9754Test
https://hdl.handle.net/1871.1/20ebcf66-2f57-433e-84da-f9b4bdad9754Test
http://www.tweelingenregister.org/publicatiesTest